Genome-wide analysis of RNA polymerase II termination at protein-coding genes

At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3’-processing of the pre-mRNA and transcription termination. Here we conduct a genome-wide analysis of this 3’-transition in yeast. We find that the 3’-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the poly-adenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and generally requires the ‘torpedo’ exonuclease Rat1 (human XRN2). The Rat1-interacting factor Rai1 contributes to RNA degradation downstream of the pA site. Defects in the 3’-transition result in transcription interference at downstream genes, which is attenuated by a back-up termination mechanism.在编码蛋白基因的末端，RNA聚合酶II（RNA polymerase II，Pol II）会发生协同转变，该过程涉及前体mRNA的3’端加工与转录终止。本研究对酵母中的该3’端转变开展了全基因组分析。研究发现，全基因组范围内的3’端转变需要RNA聚合酶II延伸因子Spt5，以及参与识别多聚腺苷酸化（poly-adenylation，pA）位点和核酸内切RNA切割的相关因子。RNA聚合酶II从DNA上的解离发生在pA位点下游的狭窄终止窗口内，且该过程通常需要“鱼雷型”核酸外切酶Rat1（人类同源蛋白为XRN2）。与Rat1互作的因子Rai1有助于pA位点下游的RNA降解。3’端转变的缺陷会导致下游基因出现转录干扰，而该干扰可通过备用终止机制得以减弱。